Investigation of metastasis related genes based on conditinoal knock out mouse model

• Project/Area Number: 25861190
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Hiroshima University
• Principal Investigator: SHIMOMURA Manabu 広島大学, 大学病院, 医科診療医 (60457249)
• Research Collaborator: HINOI Takao (10444689)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大腸癌 / 遺伝子変異 / マウスモデル

Outline of Final Research Achievements

We have generated an in vivo model system that Apc and Tgfbr2 were inactivated only in the colonic epithelium and tumors with well differentiated enocarcinoma arose mainly in proximal colon. Total RNAs of cancerous tissue areas were extracted , and we compared gene expression profiles of these mice’s tumors. We identified Gene X expression was most highly upregurated compared with control mice. The array data was validated by quantitative PCR. The cell proliferation assay revealed that silencing of X led to a significant reduction in CRC cell proliferation. Conversely, forced expression of X enhanced CRC cell proliferation in vitro. The analysis of this model revealed that Gene X is regulated by a TGFbeta signal and likely promotes cell proliferation in CRC.

Research Products

• [Presentation] マイクロサテライト不安定大腸癌マウスモデルの作製とTGF-βシグナルの同定 (2015)
  • Author(s): 三口真司、檜井孝夫、下村 学、安達智洋、斎藤保文、新津宏明、河内雅年、伊地知秀明、田中屋宏爾、大段秀樹
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2015-07-15
• [Presentation] The generation of colorectal cancer mouse model based on microsatellite instability and the identification of transforming (2015)
  • Author(s): Miguchi M, Hinoi T, Shimomura M, Tomohiro Adachi, Yasufumi Saito, Hiroaki Niitsu, Masatoshi Kochi, Yusuke Sotomaru, Hideaki Ijichi, Tsuneo Ikenoue, Kunitoshi Shigeyasu,Kohji Tanakaya, Kazuhiro Sentani, Naohide Oue, Wataru Yasui, Hideki Ohdan
  • Organizer: AACR annual meeting 2015
  • Place of Presentation: フィラデルフィア (USA)
  • Year and Date: 2015-04-18